Variant 4-55396285-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_018475.5(TMEM165):c.96G>T(p.Arg32Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000151 in 1,528,542 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00083 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000076 ( 1 hom. )

Consequence

TMEM165
NM_018475.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.113

Variant links:

Genes affected

TMEM165 (HGNC:30760): (transmembrane protein 165) This gene encodes a predicted transmembrane protein with a perinuclear Golgi-like distribution in fibroblasts. Mutations in this gene are associated with the autosomal recessive disorder congenital disorder of glycosylation, type IIk. Knockdown of this gene's expression causes decreased sialylation in HEK cells and suggests this gene plays a role in terminal Golgi glycosylation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

TMEM165 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 4-55396285-G-T is Benign according to our data. Variant chr4-55396285-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1612289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.113 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM165	NM_018475.5 link	c.96G>T	p.Arg32Arg	synonymous_variant	1/6	ENST00000381334.10	NP_060945.2	Q9HC07-1
TMEM165	XM_011534394.4 link	c.96G>T	p.Arg32Arg	synonymous_variant	1/6		XP_011532696.1
TMEM165	XM_017008412.2 link	c.-350G>T		5_prime_UTR_variant	1/8		XP_016863901.1	Q9HC07-2
TMEM165	NR_073070.2 link	n.329G>T		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMEM165	ENST00000381334.10 link	c.96G>T	p.Arg32Arg	synonymous_variant	1/6	1	NM_018475.5	ENSP00000370736.5	Q9HC07-1
TMEM165	ENST00000506198.5 link	c.96G>T	p.Arg32Arg	synonymous_variant	1/3	2		ENSP00000425449.1	D6RD79
TMEM165	ENST00000508404.5 link	n.96G>T		non_coding_transcript_exon_variant	1/7	2		ENSP00000422639.1	D6RBL0
TMEM165	ENST00000514070.1 link	n.35G>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.000829

AC:

126

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00275

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000109

AC:

AN:

128392

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

72314

show subpopulations

Gnomad AFR exome

AF:

0.00214

Gnomad AMR exome

AF:

0.000213

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000294

GnomAD4 exome

AF:

0.0000763

AC:

105

AN:

1376372

Hom.:

Cov.:

AF XY:

0.0000558

AC XY:

AN XY:

681008

show subpopulations

Gnomad4 AFR exome

AF:

0.00294

Gnomad4 AMR exome

AF:

0.000142

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.30e-7

Gnomad4 OTH exome

AF:

0.000262

GnomAD4 genome

AF:

0.000828

AC:

126

AN:

152170

Hom.:

Cov.:

AF XY:

0.000780

AC XY:

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.00274

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000641

Hom.:

Bravo

AF:

0.000865

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

TMEM165-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 08, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

TMEM165-congenital disorder of glycosylation

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 29, 2023

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

TMEM165: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

9.9

DANN

Benign

0.57

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over